Choosing from Different Treatment Options

Mark A. Socinski, MD:I think this patient is an ideal candidate for platinum-based chemotherapy. He has a good performance status. He has really no comorbid illnesses. And platinum-based therapies improve survival and do palliate symptoms, although he doesn’t really have a high symptom burden at the current time. There are a couple of options with regard to what platinum-based doublet he would be appropriate to be treated with. I think the standard of care choices would be a platinum, and that would be either a cisplatinum or a carboplatin—although in the United States, it’s almost always carboplatin. And the second drug is either pemetrexed or one of the taxanes. I think that would be considered the standard of care in a known adenocarcinoma patient.

I actually think the efficacy of those 2 choices are relatively the same. Their toxicity profile is very different. With pemetrexed, you have no neuropathy and you have very little hair loss. If those are issues or concerns, you want to avoid paclitaxel, which does have associated hair loss and the risk of neuropathy. I don’t necessarily think one is better than the other. Pemetrexed is associated with more fatigue, more anemia, and more thrombocytopenia. So, those can be sometimes concerns in individual patients.

Once we decide on the doublet aspect of treatment, the next question that I ask myself is, is the patient a candidate for bevacizumab? We have 4 positive phase III trials with bevacizumab added to platinum-based doublets that showed either increased survival or better progression-free survival. All of them showed increased response rates. So, I think in people who are eligible to receive bevacizumab, I would use it in this gentleman. I don’t see any contraindications to using it. We are told that he had a history of hypertension, but it’s well controlled on a single oral medication. He did not have any history of hemoptysis. We have clarity of his histology. His brain disease has been treated, so I would consider him clearly a pretty good candidate for bevacizumab, and I would use it either with carboplatin, paclitaxel, or bevacizumab. If there were concerns about neuropathy or alopecia, I would use it with carboplatin, pemetrexed, and bevacizumab. We know from the PointBreak trial that those 2 triplet regimens are identical with regard to overall survival.

The treatment decisions in this case are really well based in very mature phase III data. And they fall under category 1 evidence for the NCCN: the use of platinum-based doublets, the use of bevacizumab. These are category 1 NCCN recommendations. And I think they fit very well in this particular case. One of the areas of intense interest in non—small-cell lung cancer now is the role of immunotherapy. In this gentleman, at this time in the first-line setting, because he did not stain strongly for PD-L1, he is not a candidate for first-line immunotherapy.

We do have some interesting early data from KEYNOTE-021 in the cohort G, where pembrolizumab was added to carboplatin and pemetrexed and did show superior response rates, which was the primary endpoint of that rather small phase II trial and did show a benefit in PFS. The overall survival was quite immature at that particular time. That was a very exciting and enticing trial. Would I consider a small phase II trial as the basis for setting the standard of care? I would say no. I’ve always said that the oncologic highway in lung cancer is littered with positive phase II trials that failed in the phase III testing arena. So, I think we have to be encouraged by KEYNOTE-021G. But I don’t believe that that should be interpreted as being the standard of care yet.

I think all of us are interested in, will immunotherapy improve the outcomes of platinum-base doublets? Including platinum-based doublets with bevacizumab. And there is an ongoing trial that looks at carboplatin/paclitaxel/bevacizumab plus or minus atezolizumab. So, that question is being addressed. There are some theoretical data suggesting that the use of immunotherapy with anti-VEGF strategies could improve outcomes. But we have to await phase III data so we have good evidence that that’s the right thing to do.

Transcript edited for clarity.

• A 64-yr old gentleman presented with headache, impaired vision in left eye, and intermittent confusion that had begun a few weeks ago
• He is a current non-smoker with a 30-pack-year history
• Past medical history: hypertension diagnosed 3 years ago, well-controlled on losartan
• His cardiac workup is negative
• His PS by ECOG assessment is 1
• Head computed tomography demonstrated a mass (1.0 cm) in left occipital lobe with associated edema
• Full body CT scan revealed a left lower lobe lung mass (2.2 cm), and ipsilateral mediastinal lymphadnopathy
• Whole body 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan revealed increased FDG uptake in the primary left lower lobe lung mass, mediastinum, and several bony sites
• Core biopsy of the lung mass was performed and indicated
  • A histopathological diagnosis of adenocarcinoma (staining for TTF-1 was positive)
  • Genetic testing was negative for known driver mutations
  • PD-L1 testing by IHC showed expression in 15% of cells
• Brain MRI revealed 2 additional 8 mm lesions in the left frontal and right temporal lobes
• He was diagnosed with stage IV NSCLC adenocarcinoma
• He was treated with stereotactic radiosurgery (SRS) for brain metastases
• Two weeks following SRS
  • A follow up MRI scan showed no evidence of new brain metastases
  • CT scan showed:
    • 4 smaller nodules in the left upper lobe
    • The left lower lobe lung mass increased in size to 3.3 cm
    • Ipsilateral mediastinal lymph node swelling
• The patient was started on therapy with carboplatin/paclitaxel and bevacizumab